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bioRxiv · 10.1101/2025.04.16.649114

The effect of fatty acid binding protein-3 exposure on endothelial transcriptomics

Nguyen, H. C.·Singh, A.·Castellani, C. A.·Qadura, M.·Singh, K. K.
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Abstract

BackgroundFatty acid binding protein-3 (FABP3) is released in circulation following myocardial infarction and an increased level of circulatory FABP3 is also reported in peripheral artery disease patients exposing endothelial cells to higher level of FABP3. Recently, loss of endothelial FABP3 was shown to protect endothelial cells against inflammation-induced endothelial dysfunction, however, the effect of FABP3-exposure on endothelial cells is unknown. Accordingly, to study the effect of FABP3-exposure on endothelial cells we performed transcriptomic profiling following recombinant human FABP3 (rhFABP3) treatment to endothelial cells. MethodCultured human endothelial cells were treated with either vehicle or rhFABP3 (50 ng/ml, 6h) and then RNA-sequencing was performed. Gene expression analysis followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify differentially expressed genes and affected cellular functions and pathways. ResultsDifferential gene expression analysis revealed kinesin family member 26b (KIF26B) as the most upregulated and survival of motor neuron 2 (SMN2) as the most downregulated genes in rhFABP3-treated in comparison to vehicle-treated endothelial cells. Most of the differentially expressed genes were associated with endothelial cell motility, immune response, and angiogenesis. GO and KEGG analyses indicated that rhFABP3 exposure impacts several crucial pathways, prominently "Regulation of leukocyte mediated cytotoxicity" and "Natural killer cell mediated cytotoxicity", suggesting its involvement in endothelial cell physiology and response mechanisms to cardiovascular stress. ConclusionThis is the first study evaluating rhFABP3-induced transcriptomics in human endothelial cells. Our data reveal novel genes and pathways affected by FABP3-exposure to endothelial cells. Further research is necessary to validate these findings and fully understand FABP3s role in endothelial biology and in cardiovascular diseases like myocardial infarction and peripheral artery disease.

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Nguyen, H. C., Singh, A., Castellani, C. A., Qadura, M., Singh, K. K.. 2025-04-19. The effect of fatty acid binding protein-3 exposure on endothelial transcriptomics. https://doi.org/10.1101/2025.04.16.649114

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